227: 1q gain enables rescue of aneuploid hESCs during RPE differentiation

️ Episode 227: 1q gain enables rescue of aneuploid hESCs during RPE differentiation In this episode of PaperCast Base by Base, we explore This study shows that spontaneous RPE differentiation eliminates most aneuploid human pluripotent stem cells but permits expansion of cells with chromosome 1q gains when they are co-cultured with wild-type cells Study Highlights:Large-scale single-cell genomics revealed pervasive low-grade mosaicism in genetically balanced hPSC cultures, with 3–6% of cells carrying various aneuploidies. During undirected RPE differentiation most aneuploid lineages are purged, except for cells bearing gains of chromosome arm 1q which persist. 1q-gain cells only complete neural/RPE specification when co-cultured with wild-type cells that provide paracrine ligands and induce neuroectodermal regulons, enabling rescued differentiation trajectories. Rescued RPE1q cells show comparable RPE marker expression but display transcriptional signs of aneuploidy-related stress and can outcompete wild-type and other aneuploid cells, whereas 20q11.21 gains, iso20q and trisomy 20 generally fail to be rescued. Conclusion:Spontaneous RPE differentiation acts as a selective bottleneck removing most aneuploid cells but permits expansion of 1q-gain clones via wild-type co-culture rescue, underscoring the importance of genomic surveillance for hPSC-derived therapies Music:Enjoy the music based on this article at the end of the episode. Reference:Couvreu de Deckersberg E, Lei Y, Krivec N, Huyghebaert A, Duong MC, Janssens C, Regin M, Tsuiko O, Movahedi K, Verhulst S, van Grunsven LA, Sermon K, Al Delbany D, Spits C. 1q gain bypasses the selective barrier against aneuploidy in RPE differentiation via wild-type co-culture rescue. Nat Commun (2025). https://doi.org/10.1038/s41467-025-66766-w License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com Castos player https://basebybase.castos.com On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.castos.com/episodes/1q-gain-wild-type-rescue Episode Slug: 1q-gain-wild-type-rescue Keywords: aneuploidy, 1q gain, RPE differentiation, co-culture, wild-type rescue

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